The relationships among renal substrate uptake, the metabolic fates of substrates and the several renal functions in both the dog kidney in vivo and in the isolated perfused rat kidney are being studied. Since more substrate is taken up by kidney than can be oxidized, we are attempting to determine whether only certain substrates are oxidized to provide energy for renal work functions (particularly, Na reabsorption). The other substrates taken up by the kidney are utilized in such a fashion as to result in substrate conservation. This occurs by their being converted to more readily utilized or stored products than were the original substrates. The hypothesis that the products formed by the substrate interconversion mechanism can be regulated by ECF-pH is being tested. Current studies are aimed at determining whether specific substrates are utilized by certain portions of the nephron. This aspect of the problem is being probed in both the isolated perfused rat kidney and the kidney of the intact dog.